The main objectives of this project are to determine whether the cancerous lesions produced by prenatal DES injections are caused by the chemical form of DES itself or one of its metabolic products; to determine whether DES is metabolized to biologically and hormonally inactive metabolites; to test the hypothesis that certain chemicals are "transplacental toxicants" due to their relative binding to plasma/receptor proteins; to investigate some of the biochemical mechanisms which contribute to results of prenatal exposure of hormonally active environmental chemicals in the mouse; to attempt to study these same biochemical effects by tissue culture of the mouse reproductive tract; to determine the molecular locus of transplacental toxicity using structure-function relationships of different environmental chemicals, and to determine a biochemical marker for transplacental toxicity. These objectives are being studied by using refined biochemical techniques of hormone receptors and hormone action. The basic physiological effects on hormone synthesis and hormone levels will be studied using chemical extraction techniques and radioimmunoassays. Experiments to determine the carcinogenic nature of hormonally active environmental chemicals will be studied in vivo and tissue culture.